Norovirus-host interaction: Multi-selections by human histo-blood group antigens

The discovery of human histo-blood group antigens (HBGAs) as receptors or ligands of noroviruses (No Vs) raises a question about the potential role of host factors in the evolution and diversity of No Vs. Recent structural analysis of selected strains in the two major genogroups of human No Vs (GI and GII) demonstrated highly conserved HBGA binding interfaces within the two groups but not between them, indicating convergent evolution of GI and GII No Vs. GI and GII No Vs are probably introduced to humans from different non-human hosts with the HBGAs as a common niche. Each genogroup has further diverged into multiple sub-lineages (genotypes) through selections by the polymorphic HBGAs of the hosts. An elucidation of such pathogen host interaction, including determination of the phenotypes of NoV-HBGAs interaction for each genotype, is important in understanding the epidemiology, classification and disease control and prevention of No Vs. A model of this multi-selection of No Vs by HBGAs is proposed.